okay today we are going to talk about diabetes and today's first lecture is just an introduction to diabetes it is not detail of the diabetes this is just an introduction to the diabetes mellitus right with little introduction to the diabetes mellitus as a overview after that we will shift to the fundamentals right we will talk about that how blood glucose level is regulated in a healthy person within normal limits right and blood glucose level and role of different hormones hormonal interplay there are hormones which prevent the hyperglycemia and there are hormones which prevent the hypoglycemia in a normal person right so we will be talking about that too right so first of all first of all that how do you define diabetes right before we go that i want to tell you that it's something very serious you know every five second one person in the world is dying due to acute or chronic complications of diabetes again it's worth repeating it's such a serious disease that every five seconds every five seconds one person in the world is dying due to this disease i i always say that rather than saying that someone died of heart attack sometimes we should write this man died due to yes due to complications of diabetes because many of the myocardial infarctions and or end-stage renal disease or different type of strokes right right they may be induced due to complete as a complication of diabetes mellitus right so actually we can say that so many people die due to complications of diabetes mellitus right now what is really diabetes it is not one disease it is not single disease it's a group of many many diseases right and all of them are lumped together in a bag again i will say diabetes mellitus is not one single disease right it's a metabolic de-arrangement in our body this is a group of metabolic diseases and this group of metabolic diseases are put together due to certain commonalities now what are the commonalities common common thread common thread in all the diabetic patient is tendency for chronic hyperglycemia what is that tendency for yes chronic chronic hyper glycemia right this is one thing this is the common thread right or we can say that this thread is yes this thread if this i call this hyper glycemia this is a death death string chronic hyperglycemia right now second thing which is important in this group of disorders is number one yes either in there is reduced insulin production or there is resistance to the action of insulin resistance to the insulin action of insulin so we can say that all those patients who are called suffering with diabetes mellitus remember whenever i say diabetes onward i mean diabetes mellitus because there's another condition which is called diabetes incipidus that is entirely different disease that is not characterized by hyperglycemia diabetes insipidus is a condition in which there is polyurea due to reduced production of antidiuretic hormone or reduced action of antidiuretic hormone we will not be talking about diabetes and stimulators we will be talking about diabetes mellitus and when i talk about diabetes mellitus i will just mention onward diabetes so whenever i said only diabetes it means diabetes mellitus what i said up to now and diabetes mellitus it's a group of diseases common thing in all of them is hyperglycemia and in this hyperglycemia what is there either there is reduced production of insulin or there is increased resistance to the action of insulin let me put it here if this is pancreas and here are the beta cells and they produce insulin right and that is going through the blood to the cells and acting on its receptors right now either there's reduced production or there is reduced action right or any combination of both things or any combination of both things that in some of the types of diabetes writers there is reduced production as well as there is increased resistance to the action of insulin is that right now we come back let's make it right this let's make it diabetic monster right in this diabetic monster right we will put it here this is our death string here there is reduced production of reduced production of insulin i mean and here what is there increase resistance to insulin right and in this death string in this group of diseases there are many different types of diabetes for example yes the classical example in which there is reduced production of insulin is type 1 diabetes that is type one diabetes mellitus right in this case of course we'll go we'll discuss type one diabetes in detail in future but right now what i am saying the type 1 diabetes mellitus is a classical example in which there is severe reduction in production of insulin why produced why insulin is so less produced or sometimes absolutely absent because beta cells which produce insulin they have attacks by the immune system and destroyed atom or we can say that beta cells of pancreas are destroyed due to autoimmune reaction this is one example then on the other extreme we can put type 2 diabetes and type 2 diabetes the main problem is the major problem is resistance to the action of insulin at least in the initial stages of disease what is happening that beta cell the pancreas are there they might be producing insulin in normal level or even more than normal but cells are not responding to insulin right cells become deaf to the insulin right so these are the two extreme cases type one diabetes and type two diabetes classical thing and type one is there is absolute or very very dangerous reduction in production of insulin due to autoimmune destruction of beta cells of pancreas right and type 2 diabetes what we say classically in this case what happens that there is insulin is being produced at least in the early phase of disease right when because it this disease goes for many many years over decades right so at least in the beginning of the disease or early stages of the disease insulin is being produced the real problem is in the beginning that tissues are not responding to insulin is that right so these are the only two conditions or two diseases then there are more more diseases type one type two after that i can say okay someone said gestational diabetes okay we put here gestational diabetes gestational diabetes mellitus or diabetes what is this this is a condition in which during the pregnancy there is tendency for hyper glycemia or there is hyperglycemia is that right we'll discuss in detail later but what happens in gestational diabetes in this case there is problem in production of insulin as well as there is peripheral resistance that tissues are not responding well to the insulin then there is another condition with very interesting name uh we call it lada okay who will tell me lada stands for what latent yes l stands for latent autoimmune auto immune yes diabetes of adults of adults okay let me tell you now interesting thing if i talk about all the patients in the world who are suffering with diabetes mellitus and if those patients are having real problem is underlying production of insulin right most of them will be youngsters type 1 diabetes but if you find a man who is 40 year old right a man 40 year old or 50 year old and autoimmune process destroys his beta cell which is less often right so actually at a very late age he has developed autoimmune destruction of beta cell so his condition will be somewhat similar to type 1 diabetes so such patients are called not type 1 diabetes because usually this is seen in younger patients because this is very late onset of type 1 diabetes like disease this is late onset of type 1 type 1 like disease but very late onset so we call it lada right basically both are similar condition autoimmune destruction of beta cells then i would put rather than putting gestational here i will put gestational little down and again i will put something which is very similar with type 2 right which is very similar with type 2 but develops at younger age again type 1 classically develops in younger age type 2 classically develops in older age everyone knows that every good doctor knows type 1 diabetes at younger age and type 2 is at usually later age but if someone develop a disease like type 2 diabetes but at younger age is that right for example someone has diabetes diabetes mellitus in the age of 20. but his real problem is not beta cell destruction his real problem is increase resistance to the action of insulin right it means insulin is there but is unable to produce its section insulin is there but unable to produce its action so that disease but if you start at very young age classically it should start at older age if it starts at younger age we call it maturity onset diabetes mellitus right or we just call it modi what is stand for maturity onset diabetes of young people right again i will repeat and i will see will tell me the right answer first of all we talk about the two extreme this common string is hyper glycemia is that right this is the death string and it has many many death stones it has many many death stones death stones mean different types of diabetes right one extreme is type 1 diabetes in which real problem is under severe reduction in production of insulin due to autoimmune destruction of beta cells other extreme is that there is problem with the action of insulin on the peripheral tissues right and at least initially insulin is present in the patient's blood gradually it might decrease so this is type 2 diabetes so classically doctors a good doctor usually knows about type 1 diabetes and type 2 diabetes then of course there are some doctors which are very good right if we talk about very good doctor he will be aware of some slightly different situations very good doctor should be aware of that sometimes you might come across a patient who has diabetes mellitus sometimes as a doctor or as a nurse you may come across a patient who has diabetes mellitus and it is at adult age but this diabetes mellitus is behaving like type one like as if there is weird efficiency of insulin production real problem is or at least initially the real big problem is not peripheral resistance so we'll call it lada what is that latent autoimmune depth is of adults is that right so another way we can say the real difference in type 1 and ladder is one difference is that both of them are due to extreme deficiency of insulin but one is at younger age and other is that adult aid now we come to the other end every doctor knows about type 2 diabetes is that right and every doctor knows that most of the type 2 diabetes patients are at older age usually 35 40 plus but if you come across a very young person right and that person is having a type of diabetes mellitus which is behaving like type 2 diabetes it means this person is having maturity on such diabetes but in a young person this person is having maturity onset diabetes but in a young person right so we can say we have talked about four types of diabetes now we come to fifth type of diabetes we have already discussed and that was gestational diabetes gestational diabetes mellitus or diabetes then gestational diabetes is easy to understand the of course all of you must be knowing this is only limited to the females okay gestational diabetes then there is another type of diabetes which may be secondary to some situation right for example if i take some drug and that drug produces hyper glycemia and if i'm taking that drug chronically if i'm taking that drug for a long time right then what will happen that i will have a tendency for chronic hyperglycemia and we say that there is drug induced diabetes mellitus right so such kind of diabetes mellitus right they are called secondary diabetes mellitus there are so many types of secondary diabetes mellitus but just as an example we talk about one drug a very commonly used drug is beta blockers beta blockers uh classically propranolol proprana lol now propranolol it blocks basically beta receptors right and on the pancreas in the pancreas in the islet of langerhans on the beta cells there are beta2 receptors right this is pancreas here is your beta cell and on the beta cell there are yes this should be seven pass receptors this receptor is basically beta2 adrenergic receptor is that right now what happens that if you give beta blocker this receptor is not functioning right there are alpha receptors there too if these energy receptors are not functional right insulin will not be released properly there will be dysfunction in in production and release of insulin and person will develop a tendency for chronic hyper glycemia so we will say this is an example of secondary diabetes mellitus another example we can take drugs like thiazides patients who are for long term on the thiazides it's diuretic that can also produce picture like diabetes mellitus right then we can talk about some endocrine disease like cushing syndrome where chronically there is elevation of cortisol hormone right and when cortisol hormone is high chronically in your body yes cortisol harmony and glucose metabolism what cortisol is doing earth steroid hormones right what they are doing to your body as far as metabolism is concerned they produce catabolism of the proteins they produce lipolysis breakdown of the lipids so breakdown of adipose tissue and lipolysis produces free fatty acids and amino acids are also broken down due to catabolism of the proteins and both of them free fatty acids and amino acid or their derivatives they are supplied to the liver and in the liver steroids increase the process of yes gluconeogenesis and liver start producing glucose right so what we can say in cushing's syndrome there is a tendency even in acromegaly and some other endocrine diseases there is a tendency for hyperglycemia and such hyperglycemia is called secondary hyper glycemia so what did we learn up to now we just learn that diabetes is a dangerous disease and every fifth second every fifth second it is killing one person globally about 500 million people are suffering from it globally about 500 million people are suffering with the diabetes mellitus and in usa they say there are about 36 or 37 million people suffering with diabetes mellitus so when we talk talk about diabetes it puts a lot of global load there's a lot of morbidity there's a lot of mortality related with it i would say diabetes is a monster every year how many people die due to this disease who will tell me about 60 to 7 million people 60 to 7 million people die of diabetes so i must say that this is basically diabetic monster and this diabetic monster with a death string of hyperglycemia having death stones in it these death stones are different types of diabetes with two fundamental underlying process either diabetes is not being produced or the insulin is not being produced or insulin is unable to produce the effect on the tissues or both problems might occur right and type 1 diabetes insulin is insulin is not being produced and type 2 diabetes what is the real thing insulin at least at the initial stages initial gears of the disease insulin is being produced but tissues are not responding to insulin right then we talked about other types of diabetes right now why we are how diabetic skills how to habit your skills due to its dangerous complications right as i told you this our first lecture is not diabetes in detail i will talk in detail later but let us talk about this monster and this monsters complications okay first of all we should know this this is very dangerous this diabetic monster if unfortunately let's suppose we imagine a person who has diabetes for a long time he has diabetes for long time this there's not only chronic hyperglycemia because a simple doctor an innocent doctor thinks diabetes disturbs carbohydrate metabolism right but the real doctor knows that even though main problem is hyperglycemia but actually secondary to the insulin failure not only hyperglycemia occur not only carbohydrate metabolism is disturbed but protein and lipid metabolism is also disturbed severely so what we can say in this monster okay this i don't know how to make it look very angry but this in this monster a simple and innocent doctor will think that carbohydrate metabolism is disturbed but actually yes what is there lipid metabolism is also disturbed and protein metabolism is also disturbed of course we'll just we'll discuss all these disturbances in the metabolism later right in later lectures but up to now what is diabetes it's a group of diseases metabolic diseases the common thread common thing is hyperglycemia due to decreased production or decreased action of insulin or any combination of this and eventually it disturbs not only carbohydrate metabolism but protein metabolism and lipid metabolism also and i will definitely explain these things later but because it is just fundamentals of diabetes let's talk about what are the real problems with the patient right number one diabetes can produce vascular problems some people think it should be considered a disease vascular disease with many other complications right so when we talk about that diabetes damages the vessels right the vascular disease or angiopathy which occurs in the diabetic patient we divide them into two types big vessel disease and small vessel disease why we say big vessel disease as a separate group small vessel disease as a separate group big why we differentiate because underlying mechanisms are different diabetes produces big vessel disease which is called macro macro vascular complications macroangiopathy macro angiopathy or macro vascular complications or we can say big vessel diseases in diabetes mellitus and then it also produces small vessel disease right and that is called micro vascular complications or diseases complications or diseases now micro vascular means smaller vessels classically speaking capillaries but actually true definition of microbiota microvasculature is the true definition of micro vasculature is it starts from the arterioles it includes the capillaries and then venules but diabetes mellitus specifically and classically damages the pillars a lot right so there are some complications in diabetic patient due to damage to the small vessels and there are other complications which are due to damage to the big vessels large vessels large vessels mean elastic vessels elastic vessel classically your aorta or muscular arteries right so bigger vessels large vessels or mid size vessels now what are the complications it produces number one is coronary artery disease coronary artery disease right let's suppose if i talk about atheroma atherosclerosis and coronary artery disease right now what really happens you must be knowing that coronary this macrovascular disease is not specific and limited to car to diabetes mellitus it does occur with aging it does occur with the hypertension it does occur in the patient with hyperlipidemias oh it and of course it can occur in the patient with diabetes mellitus or there are unfortunate patients who have multiple factors a patient who has diabetes mellitus a patient who has hypertension patient who has unfortunately hyperlipidemias too right so he will develop coronary artery disease is that right but if you have diabetes coronary artery disease behaves very aggressively as compared to other causes of coronary artery disease let's suppose there's a person who has hypertension and here's a person who has mellitus we are uncontrolled diabetes mellitus patient with hypertension only and patients with diabetes only both of them will develop the atherosclerotic disease or multiple ethromas right but in patients with diabetes mellitus asthromas will be more severe more diffusely present and at earlier age developing for example if someone has uncontrolled hypertension only he might develop once he developed the hypertensive condition he might develop let's suppose he takes 10 years to develop dangerous ethmos but if someone has diabetes mellitus within five six years seven years he will develop very dangerous ethromas so what i am trying to say that atherosclerotic disease or atheromas in patients with diabetes they are more bigger they are more diffusely present in the vessels and they appear earlier is that right so we can say that macrovascular disease when it appears as a manifestation of coronary artery disease in the presence of diabetes disease has diseases accelerating accelerated behavior and more severe behavior and dangerous behavior right coronary artery disease of course it means in the patients with diabetes if i say coronary artery disease is more common what i really mean by this of course they have stable angina more common they have unstable angina more common they might suffer with myocardial infarction more commonly the might suffer from sudden cardiac death more commonly right i always think that someone who has diabetes and dies of the myocardial infarction i think on the gravestone it should be written this gentleman died of the complications of diabetes not just am i just to increase the awareness right so what i said that in coronary artery disease is one of the manifestation of microvascular complications and they develop in the patient very commonly right i always say i will go to the other complication let's talk about another macrovascular complication that is cerebrovascular complication cerebro vascular complications cerebral vascular events or cerebrovascular accidents what i mean by this that in patients with diabetes mellitus large vessels or medium-sized vessels either they are related with the heart or with the central nervous system they develop what kind of disease atherosclerosis they develop macroangiopathy what is diabetic macroendopathy number one diabetic microangiopathic macro is not limited to diabetes only this is can this can occur in patients with hypertension patient with hyperlipidemia or with advanced aging but once it occurs with diabetes it occurs very rapidly very severely and it is more aggressive so cerebrovascular accidents cvas related with diabetes they are very common and again cvs can be stenotic that reduced blood flow to some part of the central nervous system due to narrowing of the vessel because there is an etheroma and that if that thermo is stable but that has made the vessel narrow we can say there is stenotic cerebrovascular disease or there can be thrombotic that at the top of at the top of a throma collection of you can say platelets and fibrin right they make a mess and make the vessel very narrow may occlude the vessel and produce severe ischemia to some part of the central nervous system right so in that case we say that patient has developed thrombotic cva of course in patient with diabetes this is more common then we can come to embolic embolic events embolic events mean that maybe thrombus formed in the heart in the left ventricle and piece of a thrombus break down and it moves through blood vessels and goes to central of a system and block a vessel there so this is actually ambulance or patient has encroached vessels patient has very sphere at throma at the top of carotid atroma platelets and fiber fibrin aggregates occur and we can say a thrombus form here and that thrombus detaches from the rotated vessel and goes upward to the cerebral circulation and let's suppose it blocks the middle cerebral artery of course it will produce a very severe cva cerebrovascular accident and that will be considered embolic again i will repeat if due to diabetes a vessel in the central nervous system become narrow right we'll say this and that lead to severe damage to central nervous system that is stenotic cva or there is the ether in the central nervous system and over the throma platelet plug or thrombus form locally and this thrombus grows and closes the vessel we'll call this condition thrombotic cva or maybe carotid artery or from left ventricle or from any other major artery some thrombus flows to the central of a system right that thrombus which has detached detached from its origin and it is moving if it is moving it is no more thrombus it is ambulance and if that damages your central nervous system we say that there is embolic cva now in patients with the end then there can be of course we should not forget hemorrhagic hemorrhagic cva there can be hemorrhagic cva also and hemorrhagic cva of course there is some vessels in the central nervous system and over in that vessel very severe form of a throma dwarf and that throma damages not only entema but also damages the media and serosa so much that vessel ruptures if that vessel rupture right larger size vessel that might produce hemorrhagic severe right so in patient with diabetes again we come back there can be microvascular diseases there can be macrovascular diseases when we talk about macrovascular diseases what happens we should really focus on coronary coronary artery disease which which might clinically manifest as stable angina or unstable angina or myocardial infarction or sudden cardiac death then we should talk about other very important organ central nervous system if one of the major vessel in the central nervous system undergoes malfunction if local thrombus is formed and making the vessel very narrow we say stenotic severe if local vessel is having a trauma we call we can call it dangerous unstable malignant ethma very dangerous trauma and this is so dangerous that it is not only destroying the entire it is destroying the media and also serosa right and at the top of that at the top of that thrombus at that troma if platelets and fibrin and thrombus form then we what we will say there is from vortex and if that a throma ruptures right then hemorrhagic or if a trauma is somewhere else right and thrombose form over that for example in corroted and then thrombus detaches and becomes ambulance and this ambulance is moving in the center of the system and eventually it blocks one of the major vessels we call it emboli and if someone asks you what kind of cva is most common in patient with diabetes mellitus you must say ischemic cva what you should say ischemic cva which is classically either thrombotic or embolic right thromboembolic or thrombo thrombotic or embolic problem is that right thromboembolic disease in the central nervous system producing cva so diabetes has so many ways to kill you it can kill you by producing heart attack myocardial infarction it can damage you by producing what yes what is this producing cvs then it can prod okay can you tell me some more large vessel disease yes doctor peripheral vessel disease peripheral vessels disease we should not forget especially in the lower limb especially in the foot in the femoral arteries or popliteal arteries or even more distal arteries right in patient with diabetes very aggressive and very unstable and in big number a throw must develop as compared to the normal population right and those ethomas contribute to the diabetic foot disease because due to those traumas or a thromos with overlying thrombus right or ambulance that may lead to ischemia to the foot right we call it foot vasculopathy in diabetic patient so peripheral vascular disease can be there right and classical example is that blood flow in the lower limb in the patient with diabetes may be reduced due to complications of macro vascular yes macro vascular disease and lower limb vessels this peripheral can can develop in upper limb but less often but one thing i should not forget large vessel disease i have told you about coronary i've told you about several vascular diseases i have told you about lower limb but one special type of macro vascular disease or complication which develops in patients with diabetes is not to be forgotten you know what is that that is related with the kidney most of the doctor remember that kidney disease kidney diabetic diseases microangiopathy yes i agree to that but major vessel which supplies the kidney renal vessel that can develop a thromos multiple thrombus dangerous thrombus unstable thrombus and thrombus with thrombi which may even have emboli so we call it yes that macrovascular disease or in the renal vessel or we simply call it diabetic renal vascular disease right again in a very short way i can say that diabetes can have so many complications i was just focusing on the some of the macrovascular complications and we talked about that all of them are due to accelerated and more sphere atherosclerosis in major vessels important vessels like coronary vessels or cerebral vessels or especially in the foot or renal vessel right then we come to other group of complications right and this is microvascular complications in patients with diabetes small vessel disease up to now i told you only large vessel diseases now i'm going to tell you small vessel disease now here i want to say something very special the small vessel disease which is also called the diabetic microangiopathy what is it is called diabetic micro angiopathy this diabetic micro angiopathy is specific to diabetes what i mean by specific to diabetes that it only occurs in patient with diabetes mellitus again i will repeat when i said that there is macrovascular disease that can develop in diabetes but macrophosphoryl disease can also develop in non-diabetic patients but when i say microvascular disease a very special type of microvascular disease which specially involves the kid capillaries that people use basement membranes become very thick they build these basement membrane become very thick because their proteins are altered because there is non enzymatic attachment of glucose or glucose products with those basement membranes and those membranes proteins are altered even though microvascular capillaries baseball membrane become thick but they also become more leaky they are thick but with cracks they are thick basement membranes of the pelvis but having lot of cracks due to that reason they are very very leaky right from blood plasma proteins leak out through those basement membranes right right so don't think that if basement membrane is becoming thick it is uh actually becoming strong it is actually it is becoming thick but because it is thick due to our pathological alteration in its proteins collectively we call such altered proteins age edges what is it advanced glycation and products advance glycation end product that in the micro vessels in small vessels what really happens basement membrane become thick initially this process is reversible but over the time it becomes irreversible because these abnormalities become very stable is that right now classically and clinically if you talk about diabetic microangiopathy if you talk about diabetic micro angiopathy there are few organs which should come to your mind okay let's start from the top number one is diabetic diabetic retinopathy remember in patients with diabetes some other complications can occur due to diabetes like cataract but that is not microangiopathy right that i will discuss later what happens that microangiopathy develops in the blood vessels of retina right their retinal vessels develop thick baseball membranes and those basement membranes are not only thick but they have lot of micro cracks and through those cracks lipoproteins or lipids or proteins they leak out into retinal neuronal tissue and damage it even produce microhemorrhages right so that can end up i will say this complication what did i tell here one very dangerous situation microangiopathy yes retinal right that is micro angiopathy in the retina we simply call it retinopathy which retinopathy diabetic retinopathy later on in lectures in the future i will tell you how to differentiate diabetic retinopathy from hypertensive retinopathy this is very important as a doctor to know you know retinal vessels are the only vessels in the body which you can look directly in a healthy person there are no other vessels you can look directly right so that when you do look at the retinal vessels right you can in diabetic patient you can find abnormalities there right i will teach you later there will be a full lecture on diabetic retinopathy but right now i'm telling you there's two types of diabetic retinopathy at early stage it is not having proliferation of small vessels it's not having neovascularization but when diabetic retinopathy it become advanced what happens that new vessels sprout new vessels grow right in the retina and don't be happy every new vessel is good everything new in life is not good i have some experiences yes so these new vessels which dwell up instead in the retina even though the bunch of vessels we call it what we call it diabetic proliferative retinopathy what we call it diabetic proliferative retinopathy which occurs at advanced retinopathy these newly formed proliferative vessels a neovasculature this is super leaky and we don't want vessels to be super leaky right and when they leak there a lot they leak lot of inappropriate substances which should be limited to the blood but unduly a lot of proteins or lipids they come into neuronal tissue of the retina and produce a lot of complications we'll talk those things later but right now you just remember that one of the most important cause of blindness is diabetic retinopathy and now you are going to tell me without thinking is it a macro vascular disease or microvascular disease it is microvascular disease it is micro vascular disease micro angiopathy right number one number two after the eyes another tissue which loves to have this angiopathy that is nephropathy your kidneys you know in in kidneys you have millions of about 1.2 million nephrons in each kidney how many nephrons 1.2 million as i say in some lectures that you are millionaire as long as glomeruli of the kidneys are concerned right about 1 million to 1.2 million nephrons you have in each kidney right and in every nephron there is a bunch of capillaries which are called glomeruli those glomerular capillaries those capillaries also loves to develop microangiopathy and diabetic patient i think they love too much sweetness because they are what are this thing glomerulus the glue mirrorless there are global capillaries and capillaries are having some substance in between which is called mesengium so this capillary their basement membrane and their mesengium all of them develop advanced glycation products and that will lead to one thing that will lead to damage to the glomeruli and over the years damage to the glomeruli become what do you think this will affect more right kidney or left kidney yes doctor both kidneys of course it is hyperglycemia which is damaging of course whatever hyperglycemia is occurring in vasculature of right kidney same is on the left so this microangiopathy which develops in the blood vessels of the kidney classically in the glomeruli even though they can develop in peritubular capillaries also right they produce dysfunctional what is this they produce dysfunctional glomeruli and over the time over the years over the many years if patient is not taken care properly this angiopathy becomes so advanced that glomeruli stop functioning and person enters into end stage renal disease and in usa the most common cause of end stage renal disease is diabetes diabetic nephropathy so what i'm trying to say that this disease has so many faces to kill you it can kill you by myocardial infarction or sudden cardiac death or cerebrovascular accident or it may kill you over many many years i say this disease loves to kill its patient inch by inch this disease this master of diabetes loves to kill its patient in many different ways and over the many years an inch by inch i told you there was death string of hyperglycemia with the death stones different types and this death monster has macro vascular complications and also having micro muscular complications and when we talk about the macro vascular complication i know i'm repeating it's worth repeating that we have that patient may suffer with the heart problems or brain problems central nervous system problems or renal vascular disease or foot vasculopathy right peripheral vascular disease then it can if it does not kill at least it can make you blind that is a also very miserable situation you know there's so many beautiful things in life which you cannot see if you are blind right so it can produce blindness by diabetic retinopathy that is example of microangiopathy then we talk about diabetic nephropathy now here what is this macro vascular disease but in gloomer lye it is microvascular disease glomeruli it is microvascular disease and again i will repeat one of the most important cause of end stage renal disease especially in the advanced country that is diabetes mellitus because in poor country unfortunately many patients died due to pyelonephritis right